Biomedical Engineering Reference
In-Depth Information
be obtained. Finally, tubular or fibrillar nanostructures synthesized within the pores can be
freed from the template membrane and collected separately. Alternatively, an ensemble of
nanostructures protruding from a surface like the bristles of a brush can also be obtained
[15]. As soon as the extruded polymer solution that appears through the porous template
under water pressure comes into contact with a solidifying solution, a fiber with a diameter
dependent on the template pore size is produced (Figure 8.2B). This method is, however,
rarely used nowadays, due to its limitations in controlling fiber dimension. The resultant
fibers produced are of only a few micrometers long with diameters in the scale of a hundred
nanometers.
Phase Separation
The phase-separation technique for scaffold designing requires temperature change that
separates the polymeric solution into two phases, namely one with low polymer concentration
(polymer-lean phase) and the other with high polymer concentration (polymer-rich phase).
An appropriate liquid-liquid phase separation is critical for the preparation of nanofibers
and this does not occur in all solvents. Therefore the selection of a suitable solvent and
phase-separation temperature is crucial for the formation of nanofibers [17]. Ma and Zhang
developed a technique called thermally induced liquid-liquid phase separation for the
formation of nanofibrous structures to mimic the three-dimensional architecture of col-
lagen in natural ECM. They utilized multiple sequential steps, including the dissolution of
the polymer, liquid-liquid phase separation, polymer gelation at low temperature (which
controls the porosity of the nanoscale scaffold), solvent extraction from the gel with water,
and freezing and freeze- drying under vacuum for fabrication of the scaffold (Figure 8.2C).
Gelation was found to be the most critical step that controls the porous morphology of
the nanofibrous foams. The duration of gelation varied with polymer concentration and
gelation temperature. Nanoscale fiber networks were formed at a relatively low gelation
temperature while platelet-like (aggregates of many single crystals) structures have been
observed at high gelation temperature due to the the nucleation of crystals and their
growth. The limitation of platelet-like structure formation is overcome by increased
cooling rates that produce uniform nanofibers. However, the average diameter of fibers is
not significantly affected by gelation condition or polymer concentration. Process param-
eters such as polymer concentration were described to have a significant effect on the prop-
erties of nanofibers. An increase in polymer concentration decreased the porosity and
increased the mechanical properties of the obtained scaffolds (Young's modulus and tensile
strength). Other process parameters, such as the type of polymer, type of solvent, and
thermal treatment also influenced the morphology of the nanofibrous scaffolds [18, 19].
The advantage of the phase-separation process is that it is a relatively simple procedure
and the requirements are very minimal in terms of equipment compared with electrospin-
ning, and with self-assembly. It is possible to directly fabricate the scaffold for a desired
anatomical shape of a body part using a mold [19]. In addition, fiber density, porosity, and
mechanical properties of the nanofibrous matrices can be controlled by adjusting the
processing parameters such as the gelation temperature or polymer concentration [20].
The three-dimensional structure of pores plays an important role in determining the
quality of the tissue being developed. A combination of gelation and porogen leaching can
be used for creating a nanofibrous matrix with a macroscopic porous network. By casting
the polymer solution into a preformed mold holding a porogen, followed by subsequent
phase separation and porogen leaching, scaffolds with various pore geometries can be cre-
ated [20]. However, a relatively long time is required to obtain a batch of nanofibrous foam
and it is also difficult to obtain long continuous fibers by using this process [21]. Moreover,
this method is only capable of producing nanofibers from polymers with gelation ability.
